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Apparatus and method for detecting flinch response to nociceptive agents

Inactive Publication Date: 2006-02-07
UNIV OF CALIFORNIA SAN DIEGO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0012]The current passing through the transmitter coil typically generates an electromagnetic field in the 6 to 8 kilohertz range with a signal strength on the order of 5 to 8 milliwatts. The metal object attached to the animal's paw is a small metal annular collar that fits around the paw. The object can also be a small metal “C” collar in incomplete annular form. The metal object can be made of, or contain a ferrous metal. The metal object can also be non-ferrous. The observation chamber is

Problems solved by technology

An important limitation of this behavioral model is its labor-intensive nature regarding data collection and the time required to train observers in its reliable implementation.
Though of merit, these approaches are limited in that each only indirectly measure movement of the injected paw.

Method used

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  • Apparatus and method for detecting flinch response to nociceptive agents
  • Apparatus and method for detecting flinch response to nociceptive agents
  • Apparatus and method for detecting flinch response to nociceptive agents

Examples

Experimental program
Comparison scheme
Effect test

example 1

Formalin Induced Behavioral Response

[0076]The injection of formalin into the dorsum of one hind paw of 100 male Sprague Dawly rats over a period of 10 months showed a reliable biphasic flinching of the injected paw, with peak flinch rates during Phase I and II being on the order of 50 flinches / min and 37 flinches / min. FIG. 7 presents the time course of flinch responses, the mean cumulative flinches observed by Phase (Phase I: 203±9 SEM; II: 1058±39 SEM; IIA: 792±27 SEM; and IIB: 266±16 SEM); and the statistical distribution of flinching in Phase I and II. Analysis of this distribution (Kolmogorov-Smirnov) indicates that each Phase was distributed normally (p>0.9999).

System Stability and Reliability

[0077]Separate groups of 4 male Holtzman Sprague Dawley rats were run in the morning (AM) and afternoon (PM) on 5 consecutive days. The following summarizes comparisons of the data.

[0078]Comparison Between Test Chambers

[0079]There was no difference in the scores for Phase I, II, IIA or IIB...

example 2

Characterization of the Variables Influencing the Formalin Response

[0087]Morning (AM) Versus Afternoon (PM) Test Periods.

[0088]Examination of flinching behavior in the morning (08:00–10:00) and in the afternoon (15:00–17:00) over 5 days of testing showed no difference between AM and PM for all four phases (Table 5). There were no differences across time of day for any phase (1-way ANOVA, p>0.10 to 0.99).

[0089]

TABLE 5Cumulative flinching behavior (Mean ± SD) as a function of testingtime, by phase.GROUPNPhase IPhase IIPhase IIAPhase IIBAM20129 ± 55684 ± 210506 ± 141179 ± 103PM20129 ± 60797 ± 293586 ± 186212 ± 134

[0090]Effects of Body Weight on Flinching Behavior.

[0091]Three groups of rats differing in body weight (125–175 grams, 300–350 grams and 400–450 grams) were examined for flinching behavior. No difference in flinch response was observed in Phase I, II and IIA (1-way ANOVA, p>0.05). A weight-related difference was seen in the flinching behavior for Phase IIB (1-way ANOVA, p<0.05...

example 3

Effects of Systemic and Spinal Drugs on Formalin Evoked Flinching Behavior

[0103]Morphine.

[0104]Intrathecal and systemic injection of morphine (μ opioid agonist) resulted in a potent dose dependent reduction of all phases of the flinching response (FIG. 10). The ED50 values were calculated using least squares linear regression analysis of the dose effect (% Maximum Possible Effect, % MPE) curves (Table 11).

[0105]MK801. Intrathecal and systemic injection of MK801 (a noncompetitive NMDA receptor antagonist) resulted in a potent dose dependent reduction in Phase II but not Phase I of the flinching response (FIG. 11). The ED50 values were calculated using a least squares linear regression analysis of the dose effect (% Maximum Possible Effect, % MPE) curves (Table 11).

[0106]

TABLE 11ED50 values for the effects of systemic morphine, intrathecalmorphine and MK801 on flinching behavior (Mean and 95%confidence intervals)*GROUPPhase IIPhase IIAIT Morphine (μg)1.6 (0.6–4.7)1.5 (0.6–3.6)IP Morph...

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PUM

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Abstract

An apparatus and method for measuring spatial displacement of an animal's paw injected with irritant. This apparatus comprises an electromagnetic detecting assembly having (1) a transmitting oscillator for generating electrical current (2) an electromagnetic transmitter coil coupled to the oscillator for generating an electromagnetic field (3) an electromagnetic receiving coil placed in axial plane directly below the transmitter coil (4) a first, receiving amplifier connected to the receiving coil (5) an amplitude detector connected to the receiving amplifier (6) a second amplifier connected to the amplitude detector (7) a metal object attached to the animal's paw (8) and a cylindrical observation chamber of a diameter not greater than the diameter of the generated magnetic field.

Description

BACKGROUND OF THE INVENTION[0001]1. Field of the Invention[0002]The present invention concerns detection of response to nociceptive pain. This invention particularly concerns an automated model for screening anti-nociceptive agents by detecting and measuring a flinch response in an animal whose extremity has been subjected to an irritant such as formalin.[0003]2. Description of the Prior Art[0004]The escape response or agitation evoked by a transient, strong stimulus attests to there being a close relationship between stimulus intensity, peripheral afferent discharge and magnitude of the pain state as defined by response latency and magnitude. There are situations, however, in which the magnitude of the response to pain may exceed what would normally be anticipated given the magnitude of the physical stimulus and the afferent traffic generated by that stimulus (31, 45, 47). These situations are loosely considered as reflecting a state of hyperalgesia, possibly arising from sensitiza...

Claims

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Application Information

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IPC IPC(8): A61B5/05A61B5/11G01D5/20
CPCA61B5/1105A61B5/4884G01D5/2046A61B2503/42A61B5/6824A61B2503/40
Inventor YAKSH, TONYOZAKI, GEORGE
Owner UNIV OF CALIFORNIA SAN DIEGO
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